FDA Approves Imfinzi Plus Chemotherapy for Patients with Advanced Biliary Tract Cancer

The U.S. Food and Drug Administration approved AstraZeneca’s Imfinzi as the first immunotherapy regimen for the treatment of adult patients with locally advanced or metastatic biliary tract cancer in combination with chemotherapy.

Photo: Dave Fredrickson, executive vice president of the Oncology Business Unit of AstraZeneca

“For the first time, patients in the United States with advanced biliary tract cancer have an immunotherapy-based treatment option that meaningfully extends survival and is well-tolerated,” said Dave Fredrickson, executive vice president of the Oncology Business Unit of AstraZeneca.

The approval was based on the results from the TOPAZ-1 phase 3 trial. In an interim analysis of TOPAZ-1, Imfinzi plus chemotherapy (gemcitabine plus cisplatin) reduced the risk of death by 20 percent versus chemotherapy alone. An estimated one in four patients treated with Imfinzi plus chemotherapy were still alive at two years compared to one in 10 treated with chemotherapy alone. Results were consistent across all prespecified subgroups, regardless of PD-L1 expression or tumor location.

Biliary tract cancer (BTC) is a group of rare and aggressive gastrointestinal cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder, or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine). Cholangiocarcinoma is more common in China and South-East Asia and is on the rise in Western countries. Gallbladder cancer is more common in certain regions of South America, India, and Japan. Approximately 23,000 people in the United States are diagnosed with BTC each year. These patients have a poor prognosis, with approximately 5 percent to 15 percent of patients with BTC surviving five years. Early stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage when treatment options are limited, and the prognosis is poor.

Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

“This approval represents a major step forward for patients with advanced biliary tract cancer, who urgently need new, well-tolerated and effective treatment options after more than a decade of limited innovation,” said Aiwu Ruth He, associate professor of Medicine, leader of the GI Cancer Program, Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington DC, and a lead investigator in the TOPAZ-1 phase 3 trial.

TOPAZ-1 is a randomized, double-blind, placebo controlled, multicenter, global phase 3 trial of Infinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centers across 17 countries including in the United States, Europe, South America, and several countries in Asia including South Korea, Thailand, Japan, and China.

The TOPAZ-1 phase 3 trial results were presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium and published in the New England Journal of Medicine Evidence. Imfinzi plus chemotherapy was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.

In July 2022, Imfinzi plus chemotherapy was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a Category 1 preferred regimen as 1st-line therapy for locally advanced or metastatic BTC based on the data from TOPAZ-1.

The U.S. regulatory submission for TOPAZ-1 was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Imfinzi plus chemotherapy is also under regulatory review for the same indication by the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration, Singapore’s Health Sciences Authority, Switzerland’s Swissmedic and the UK’s Medicines and Healthcare products Regulatory Agency.

The approval was granted after securing Priority Review and Orphan Drug designations for Imfinzi in the U.S. in this setting. Regulatory applications are also currently under review in Europe, Japan, and several other countries based on the TOPAZ-1 results.

In addition to the approval in BTC, Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage 3 non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy and is the global standard of care in this setting based on the PACIFIC Phase 3 trial.

Imfinzi is also approved in the United States, European Union, Japan, China, and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN phase 3 trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone. Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

Author: Rare Daily Staff